Catalysis of Salicylaldehydes and Two Different <i>CH</i> Acids with Electricity: First Example of an Efficient Multicomponent Approach to the Design of Functionalized Medicinally Privileged 2‐Amino‐4<i>H</i>‐Chromene Scaffold

Abstract

Abstract Electrochemically induced multicomponent transformation of salicylaldehydes and two different CH acids in alcohols in an undivided cell in the presence of sodium bromide as an electrolyte results in the efficient and selective formation of diversely functionalized, medicinally privileged 2‐amino‐4 H ‐chromene scaffolds in 65–86% yields. The developed electrocatalytic system affords the distinction between two CH acids according to their reactivity, and offers an efficient approach to the 2‐amino‐4 H ‐chromene scaffold with a predefined arrangement of desired substituents. The electrocatalytic multicomponent reaction smoothly proceeds with salicylaldehydes bearing both electron‐donating and electron‐withdrawing groups. Thus, fifteen previously inaccessible, close structural analogues of the tumor antagonists HA14‐1 and MX58151 have been synthesized. The electrocatalytic process was found to be advantageous in terms of selectivity and yields compared to classic chemical base catalysis, and includes a remarkable mechanistic feature that is promising for the further development of 2‐amino‐4 H ‐chromene chemistry. The application of this convenient electrocatalytic multicomponent method to the formation of medicinally relevant 2‐amino‐4 H ‐chromenes is also beneficial from the viewpoint of diversity‐oriented large‐scale processes and represents a novel, facile and environmentally benign synthetic concept for multicomponent reaction strategy.